Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction

BackgroundIn reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI.MethodsAdult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n = 8), pVEGF (n = 8), EPO (n = 8) or placebo (n = 8).ResultsFifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF + EPO: 8 ± 1%; pVEGF: 16 ± 5%; EPO: 13 ± 4%) compared to placebo (25 ± 7%, p < 0.001). However, in the EPO + VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p < 0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect.ConclusionsCombined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.